Automomic

Pharmacology

DR. APURBA BISWAS

MEDICAL OFFICER,
UPAZILA HEALTH COMPLEX, TUNGIPARA,
GOPALGANJ
ATTACH: MATS ,TUNGIPARA ,GOPALGANJ
 Nervous
System

CNS PNS
Sympathetic division:
Thoracolumbar outflow (T1-L2)

Parasympathetic division:
Craniosacral outflow.
Cranial: III, VII, IX, X, and Sacral: S2,3,4
 Cholinergic receptors

Cholinergic receptors are of two types -

a) Muscarinic receptors (subtypes: M1, M2, M3)
b) Nicotinic receptors (subtypes: N1, N2)
Pharmacological action of Acetylcholine

Muscarinic action:

 On cardiac muscle:
Depress cardiac muscle by stimulating vagus nerve and
produce -
a) "-ve" inotropic action: Decrease force of contraction.
b) "-ve" chronotropic action: Decrease heart rate
(Bradycardia).
c) Decrease stroke volume and cardiac output.

The net effect: fall of blood pressure

 On smooth muscles:

Contraction of smooth muscles except

vascular and sphincteric smooth muscles.
 On Eye:

 Miosis (due to contraction of circular muscle).

 Decrease intraocular pressure (by increasing
the drainage ocular fluid through the channel of
Schlemn).
 Increase lacrimal secretion (tear).
 On Lungs:

 Bronchoconstriction.
 Increase bronchial secretion.

 On GIT:
 Increase HCI secretion
 Increase intestinal secretions
 Increase motility (diarrhoea)
 Sphincter relaxation.
 On Gallbladder and Bile duct: Contraction.

 On urinary bladder:
•Contraction of detrusor muscle
• Relaxation of sphincter (promote micturition)

 On Uterus: Contraction of uterine muscle.

• Increase motility (diarrhoea)
• Sphincter relaxation.
 EXCEPTIONS
 On blood vessels: Relaxation of vascular
smooth muscles-vaso-dilation → Decrease
total peripheral resistance (decrease BP).

 On sphincter: Relaxation of sphincters of

GIT and urinary bladder.
 On exocrine glands: Increase secretion of –
• Salivary glands (watery secretion)
• Gastric glands
• Bronchial, intestinal glands
• Lacrimal glands
• Pancreatic and sweat glands.
 Nicotinic action:
 CVS (Sympathetic autonomic stimulation):
 Tachycardia.
 Increase blood pressure.

 GIT (Parasympathetic stimulation):

 Increase motility
 Increase secretion

 Urinary bladder: Promote micturation.

 On skeletal muscles (neuromuscular junction): Muscle

fasciculation.
 On CNS:
 Excitation followed by depression
 Anxiety
 Restlessness
 Insomnia.
 CHOLINERGIC DRUGS

Cholinomimetic Drugs
Drugs, which act on acetylcholine receptors and evoke
response similar to those, produced by acetylcholine and
to those, which result from cholinergic nerve stimulation,
are called cholinergic drugs.

Direct-acting cholinomimetic agents bind to and activate

muscarinic or nicotinic receptors.
Indirect-acting cholinomimetic agents produce their
primary effects by inhibiting acetylcholinesterase, which
hydrolyzes acetylcholine to choline and acetic acid.
Classification of Cholinergic Drugs

Direct acting
 Choline esters:
• Acetylcholine
• Methacholine
• Carbachol
• Bethanechol
 Natural cholinomimetic alkaloids:

• Pilocarpine
• Arecoline
• Muscarine
• Nicotine
Indirect acting
 Reversible:

• Physostigmine
• Neostigmine
• Pyridostigmine Endrophonium
 Irreversible: (OPC)

a) Alkyl-phosphate group:
• TEPP (tetra-ethyl pyro-phosphate)
• HETP (hexa-ethyl tetra-phosphate)
• DFP (di-isopropyl fluro-phosphate)
• OMPA (octa methyl pyrophosphor amide)
b) Aryl group:
• Chlorothion
• Malathion
• Parathion
 CHOLINE ESTERASES (ChE)

Group of enzymes which hydrolyse the cholinesters, are called

choline esterases (ChE). Such as-

Cholinesterase
Acetylcholine Acetic acid + Choline +
ChE
 ANTI-CHOLINESTERASE
(ChE inhibitor)

 Drugs which inhibit the enzyme cholinesterase

and so increase the cholinergic activity are
called anticholine-sterase.

 Anti-ChE inhibits the enzyme cholinesterase.

 Prevents hydrolysis of acetylcholine, and so
Increase acetylcholine concentration at
cholinergic sites.
So, Anti-ChE are called indirectly acting
cholinergic drugs.
 Types of Anti-ChE

Reversible Anti-ChE
 Physostigmine
 Neostigmine
 Pyridostigmine
 Endrophonium
Irreversible Anti-ChE OP-compound
 DFP, TEPP, HETP
 Malathion
 Parathion,
 Diazenon
 Organophosphorus compounds (OPC)

1. Alkyl phosphates:
•Hexa-ethyl-tetra-phosphate (HETP).
• Tetra-ethyl-pyro-phosphate (TEPP).
2. Aryl phosphates:
•Dithione.
• Malathion.
•Parathion.
•Diazinon.
Criteria of OPC:

1. Binds with cholinesterase enzyme

irreversibly due to formation of covalent bond.
2. Highly lipid soluble.
3. Absorbed from skin, lung, GIT & CNS.
4. Use: Insecticide, suicidal & homicidal.
 Clinical features of OPC poisoning:

1. Eye : Miosis (pin-point pupil).

2. CVS: Bradycardia, hypotension
3. Respiratory : Bronchorrhoea, bronchoconstriction,
cough, wheeze, dyspnoea
4. GIT: Diarrhoea, vomiting, abdominal cramps,
hyperacidity (heart burn)
5. Urinary: Urinary urgency (↑ frequency of micturition).
6. Exocrine: : Profuse sweating & salivation.
7. CNS: Tremor, restlessness, convulsion, hypothermia,
respiratory centre stimulation.
8. Skeletal muscle: Flaccid paralysis of skeletal muscles
lead to weakness, twitching (nicotinic action).
 Management of OPC poisoning:
1. Immediate hospitalization of the patient.
2. General measures:
 Remove the patient from the contact of poison.
 Remove the contaminated clothing and wash the contaminated skin by
soap and water.
 Clearance of airway and mouth.
 Stomach suction with 2% KMnO4: If patient comes within 4-hours of
poisoning.
 O2 administration in high dose (4-6 litres/min).
 Keep the patient NPO (nothing per oral).
 Open /v channel & give /v fluid, e.g. 5% DA or DNS..
 Broad-spectrum antibiotic (if secondary infection).
 Diazepam (if convulsion present).
 Sodi-bi-carb (NaHCO3): if metabolic acidosis present.
3. Atropinization:
 Catheterization (before giving the 1st dose of Atropine).
 3-5 amp Atropine v stat & then the double dose should be
given in every 5-10 minutes interval until full atropinization.
 If full atropinization occurs - then 3 amp Atropine is repeated at
a longer (8-hourly) interval for at least 48-72 hours.
4. Specific measures: (If patient comes within 6-hours of
poisoning)
• Inj. Pralidoxime (specific antidote) 30 mg/kg /v over 10 minutes
and may be repeated every 1⁄2 hourly and then 8-hourly for 48-72
hours.
5. Follow up:
 After discharging from the hospital, the patient should be
advised to take rest for at least 6 weeks for re-synthesis of the
cholinesterase enzyme.
 Patient should be advised to consult with a psychiatrist after
discharge.
 Atropinization

Definition of atropinization:

The signs produced after atropine administration in

OPC poisoning, are called atropinization. In OPC
poisoning, IV Atropine should be continued until full
atropinization & then atropine should be stopped,
otherwise there is chance of atropine toxicity.
Signs/features of atropinization:

1. Dilated pupil.
2. Dry eye.
3. Dry mouth.
4. Dry skin.
5. Reduced rhinorrhoea.
6. Increased pulse rate.
7. Urinary retention (signs of toxicity).
8. Pyrexia (signs of toxicity).
 Anti-cholinergic drugs

Definition of anti-cholinergic drugs:

Drugs which blocks the pharmacological actions

of cholinergic drugs are called anti-cholinergic
drugs.
Classification of anti-cholinergic drugs:

A. Anti-muscarinic drugs (muscarinic receptor blockers).

B. Anti-nicotinic drugs (nicotinic receptor blockers):
1. Ganglion blockers.
2. Neuromuscular blockers.
 Anti-muscarinic drugs

Definition of anti-muscarinic drugs:

Drugs that competitively antagonize the actions of acetylcholine

at muscarinic receptors are called anti-muscarinic drugs.

Example:
1. In CVS disorder/ pre-anaesthetic medication: Atropine
2. Anti-asthmatic: Ipratropium bromide
3. Anti-spasmodic:
Hyoscine-N butyl bromide,
Tiemonium Methylsulphate
 Atropine

Atropine reversibly competes with

muscarinic receptor of acetylcholine
and antagonises the muscarinic action
of acetylcholine.
 Pharmacological action of Atropine
 On smooth muscle: Relaxation of all smooth muscle:

 GIT : Reduction of tone and peristalsis.

 Lungs : Relaxation of bronchial smooth muscle.
 Bladder : Relaxation of detrusor muscle (urinary retention)

 Ocular effects:

 Mydriasis : Pupillary dilatation.

 Photobhobia: Due to wide pupillary dilatation.
 Cycloplegia: Paralysis of accommodation for near vision (by paralysis of ciliary muscle).
 Increase IOP : In glaucoma, not significant in normal individual
 Light reflex: Lost (unresponsive pupils)
 Pupillary size: Unequal.

 CNS effects:
 Stimulation of CNS. Agitation, restlessness

Hallucination, disorientation Anti-parkinsonism-like action

 CVS effects: Bradycardia followed by tachycardia.
Bradycardia: Due to CNS vagal stimulation. Tachycardia: Due
to antimuscarinic effects.

 Blood vessel: No significant action (therapeutic dose).

 Exocrine glands: Diminishes secretions.

Salivary: Decrease salivation (dry mouth)
Lacrimal : Decrease lacrimation (dry eye).
Sweat gland: Decrease sweating (dry skin)
Gastric: Decrease HCl secretion.
Bronchial : Decrease bronchial secretion. (Mammary): No effect.
Indications of atropine:

1. Treatment of OPC poisoning.

2. As anti-spasmodic:
• Gastrointestinal colic.
• Ureteric & biliary colic.
• Peptic ulcer.
• Acute pancreatitis & acute abdomen.
• Dysmenorrhoea.
3. As mydriatics and inflammatory conditions of eye.
4. As pre-anaesthetic medication for bronchodilator & to reduce bronchial
secretion.
5. As anti-parkinsonism.
6. As anti-motion sickness.
7. Treatment of sinus bradycardia after MI.
8. Excessive sweating (Hyperhidrosis).
Contraindications of atropine:
1. Acute congestive glaucoma.
2. Congestive cardiac failure.
3. Prostatic enlargement (urinary retention).
4. Gastric outlet obstruction (pyloric stenosis).
5. Chronic lung disease.
 Adverse effects of atropine:

1. Skin:
• Hyper-pyrexia (109°F).
• Dryness of skin.
2. GIT:
• Dryness of mouth.
• Hoarseness of voice.
• Constipation.
3. Eye:
• Blurring of vision.
• Mydriasis.
• Cycloplegia.
• Loss of light reflex.
• Glaucoma.
4. CVS:
• Tachycardia..
• Palpitation.

5. Bladder:
• Retention of urine.

6. Lung: Quick & shallow respiration.

7. CNS:
• Restlessness.
•Agitation.
•Excitement.
• Convulsion.
• Confusion.
• Hallucination.

8. Allergic reaction:
• Dermatitis.
• Conjunctivitis.
• Eyelid swelling.
Classical clinical features of atropine poisoning:

1. Red as a beet (skin flushed).

2. Hot as a hare (hyperthermia).
3. Dry as a bone ((dry mucous membrane, no
sweating).
4. Blind as a bat (cycloplegia, blurring of
vision).
5. Mad as a hatter (confusion, delirium).
ADRENERGIC DRUGS

SYMPATHOMIMETIC DRUGS)
(

Drugs that mimic the effects of stimulation of

sympathetic nervous system are called adrenergic
drugs.
Types of adrenergic receptors:

There are three types of adrenoceptors:

α adrenoceptor (subclasses: α1, α2)
β adrenoceptor (subclasses: β1, β2, β3)
Dopamine receptors (D1, D2).
 Pharmacological action of adrenergic agonist

CVS ↑ heart rate.

↑ force of contraction.
↑ tissue perfusion (dopamine)

Blood vessels Vasoconstriction (α)

Vasodilatation (β)
Lungs Bronchodilatation (β)
Nerve terminal : Inhibit nor-adrenaline release (α).
This is called auto-inhibitory feedback
mechanism of nor-adrenaline release.
 Classification of adrenergic drugs

According to receptor selectivity

1) α1 - agonist: 6) Both β1 & β2 agonist
Phenylephrine
Methoxamine
2) α2 -agonist: 7) Both α & β agonist
Clonidine
a-methyl noradrenaline
3) Both α1 - α2 agonist:
Adrenaline.
Noradrenaline
4) β1 -agonist:
Prenalterol
• Dobutamine
5) β2 -agonist:
Salbutamol
Terbutaline
Orciprenaline
According to therapeutic utility
 Vasoconstrictors:
• Adrenaline
• Noradrenaline
• Ephedrine
• Metaraminol
 Bronchodilators:
• Salbutamol
• Terbutaline
• Orciprenaline
 Salbutamol

Selective ẞ2 agonist (Bronchoselective).

Indications of salbutamol:

1. Bronchial asthma.
2. Chronic bronchitis.
3. Emphysema.
4. Bronchospasm.
5. Exercise induced asthma.
6. Threatened abortion (as it causes relaxation of
uterus).
Contraindications of salbutamol:

1. Hyperthyroidism.
2. Ischaemic heart disease (IHD).
3. Diabetes mellitus.
4. Lactating mother.
5. Parkinsonism.
6. Hypokalaemia.
7. Hypotension.
8. Severe weakness and collapse condition.
Adverse effects of salbutamol:

1. Due to chronic inhaler use:

•Dryness of airway.
• Irritation of airway.
• Oropharyngeal candidiasis.

2. Due to systemic use (oral):

• Tremor.
• Tachycardia.
• Palpitation.
• Hypotension.
• Hypokalaemia
• Headache.
• Drowsiness.
• Dizziness.
• Nervousness.
• Weakness.
 ANTI-ADRENERGIC DRUGS

Synonyms
1) Adrenergic blockers
2) Sympatholytics
3) Sympathoplegic drugs

Definition :
Drugs that inhibit the action of catecholamines and
other adrenergic agonists, are celled anti-adrenergic
drugs.
Classification of Anti-adrenergic drugs

 Adrenergic receptor blockers.

 Adrenergic neuron blockers.
Classification of adrenoceptor antagonists

β-antagonist
α-antagonist
β1 -selective:
α1 -selective:
• Prazosin • Atenolol
• Terazosin • Acebutol
• Indoramin • Proctolol

α2-selective:
β2-selective:
• Yohimbine
• Idazoxan • Butoxamine

Non-selective (α1 / α2): Non-selective (β1 / β2)

• Phenoxybenzamine
• Propranolol
• Phentolamine
• Tolazoline • Timolol
Adrenergic Neuron Blocker

Drugs that deplete catecholamines or prevent

their release at adrenergic neurons are called
adrenergic neuron blocker.

Example:
Synthesis blocker: α – methyl dopa
 Propranolol
Pharmacological action of propranolol:

Effects on CVS: It has got three effects-

a) Anti-hypertensive effect: ↓ Heart rate & force of

contraction →↓ Cardiac output →↓ BP.

b) Anti-arrhythmic effect: Automaticity→↓ conduction

velocity → ↑ Refractory period →anti-arrhythmia.

c) Anti-anginal effect: Decrease myocardial activity →

Reduce the myocardial O2 demand. Decrease blood
pressure → so, ↓ O2 demand.
2. Effects on lungs:
• Bronchoconstriction.
3. Effects on kidney:
↓ Renin secretion →↓ angiotensin-II mechanism →
renal vasodilatation and ↓ salt & water retention →↓ BP.
4. Effects on eye:
• Reduce intraocular pressure (IOP) by decreasing
aqueous humor production.
5. Effects on metabolism:
• Decrease blood glucose level by inhibiting
glycogenolysis (impair recovery from hypoglycaemia).
• Fat cell: Lipolysis →↓ FFA level→ dyslipidaemia.
6. Effects on CNS: Tranquillisation.
 Indications of propranolol:

A. Cardiac:
1. Treatment of hypertension.
2. Cardiac arrhythmia.
3. Anginal pain.
4. Myocardial infarction (later stage).
5. Hypertrophic obstructive cardiomyopathy.
6. Fallot's tetralogy.
7. Portal HTN and oesophageal varices.

B. Neurologic:
1. Migraine prophylaxis.
2. Anxiety states.
3. Tremor.
4. Alcohol & opioid withdrawal syndrome.

C. Endocrine: Hyperthyroidism.

D. Eye: Glaucoma.
Contraindications of propranolol:

A. Cardiac contraindications: mifested as:

1. Heart block.
2. Congestive cardiac failure (CCF).
3. Recent MI.
4. Bradycardia.
5. Hypotension.
6. Peripheral vascular diseases (e.g. Buerger's disease).

B. Non-cardiac contraindications:
1. Bronchial asthma.
2. Dyslipidaemia (poor lipid profile).
3. Diabetes mellitus.
4. Pregnancy.
5. Chronic obstructive pulmonary disease (COPD).
Adverse effects of propranolol:

1. CVS:
• Bradycardia.
• Hypotension.
• Heart failure,
• Reduced peripheral blood flow.

2. CNS:
• Sedation.
• Sleep disturbance (Insomnia, night mares).
• Depression.
• Suicidal tendency (in case of long-term use).

3. Others:
• Bronchoconstriction.
• Dyslipidaemia
• Insulin dependent DM (IDDM): Symptoms of hypoglycaemia will not occur, the patient misses the
warning symptoms of hypoglycaemia & turn into coma.
• Fatigue.
• Sexual dysfunction in men.
 Adrenergic neuron blockers

α -methyl dopa / methyl dopa

Indications of α-methyl dopa / methyl dopa:

1. Moderate & severe hypertension.

2. Pregnancy with HTN.
3. Hypertensive crisis.
4. Pheochromocytoma.
5. Malignant carcinoid.
6. Pre-eclampsia.
7. Eclampsia.
Contraindications of a-methyl dopa / methyl
dopa:

1. Severe liver damage.

2. Severe kidney damage.
3. Lactating mother.
4. Haemolytic anaemia.
5. Parkinsonism.
6. Psychiatric disorder.
7. Severe hypotension.
8. Generalized oedema.
9. Electrolyte imbalance.
10. Hypersensitivity to methyl dopa.
Adverse effects of a-methyl dopa / methyl dopa:
1. M = Mental symptoms (sedation, drowsiness,
nightmares, vertigo).
2. E = Electrolyte imbalance.
3. T = Tolerance, thrombocytopenia.
4. H = Headache.
5. Y = Psychic depression.
6. L = Lactation (due to prolactin release).
7. D = Dryness of mouth.
8.O = Oedema
9. P = Parkinsonism, postural hypotension.
10. A = Allergic reaction,